tbuckley/cabot-search huggingface dataset:
Korean Precision Medicine Networking Group study of molecular profiling guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) II (KCSG AL 22-09).
Authors: Sun Young Kim, Jee Hyun Kim, Tae-Yong Kim, Sook Ryun Park, Shinkyo Yoon, Soohyeon Lee, Se-Hoon Lee, Tae Min Kim, Sae-Won Han, Hongseok Yun, Sejoon Lee, Jihun Kim, Yoon-La Choi, Kui Son Choi, Heejung Chae, Hyewon Ryu, Gyeong-Won Lee, Dae Young Zang, Joong Ahn
Journal: Journal of Clinical Oncology (2023)

TPS1608 Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions as molecular diagnostics for cancers since 2017, when it was reimbursed by the National Health Insurance Service. However, molecularly-guided treatment (MGT) options based on NGS results have been limited due to the strict regulation for prescribing outside of the approved indication, lack of clinical trial availability, and limited access to molecular tumor boards (MTB) in most institutions. Given our previous KOSMOS study results, which showed MGT was available for 54% (124/198) of patients based on local NGS (ESMO Open 2022;7(6, Suppl 1);100653), KOSMOS-II study was designed to demonstrate MGT would be feasible and effective via a nation-wide precision medicine platform. Methods: This national, prospective, pragmatic, multi-cohort study comprised of a framework to screen pts with metastatic solid tumors for actionable genetic alterations (GA) based on local NGS testing and to recommend MGT by a remote and centralized MTB held weekly or biweekly. MGT can be one of the following options: Tier 1, the therapeutic use of investigational drugs targeting GAs including ALK, EGFR, ERBB2, BRAF, FH, ROS1, RET, or high tumor mutational burden; Tier 2, drugs that are allowed for treatment outside of the approved indications by the National Health Insurance; Tier3, clinical trials matched for GA recommended by MTB. To estimate the proportion of patients receiving MGT to be 50±3.25% with 95% confidence interval, we will enroll 1,000 pts, considering 5% drop-out rate. The clinical benefit rate of MGT beyond 16±2 weeks is the second co-primary endpoint, which is expected to be 30% with type I error of 5% and 90% power. Pts must have progressed ≥ 1 or more lines of therapies; have undergone NGS testing; are able to provide the Variant Call Format (vcf) file of the NGS results. MTB determines clinical actionability of GA and recommends MGT if possible, according to Tier 1,2, or 3. The vcf files and matched clinical information will be deposited to the repository of National Center Center Korea and will be curated in a de-identified clinico-genomic database. As of Feb 2023, 139 of planned 1,000 have been enrolled. Clinical trial information: NCT05525858 .
Trends in Medicare utilization and reimbursement for hematology/oncology procedures.
Authors: Julijana Zoran Conic, Thomas Reske
Journal: Journal of Clinical Oncology (2023)

e13641 Background: Medicare Part B pays for physician services such as office visits and procedures based on the Medicare Physician Fee Schedule which is re-evaluated annually to maintain budget neutrality. Moreover, national cancer-attributed medical care costs in 2015 were $183 billion and projected to increase 34% to $246 billion by 2030 (Green et al: J Clin Oncol, PMID: 31804856). The aim of this study is to evaluate trends in Medicare reimbursement for procedures in hematology/oncology between 2012-2022. Methods: The data analyzed were extracted from the Physician Fee Schedule Look-Up Tool. CPT Codes were obtained from the Medicare Coverage Database. The following CPT codes were extracted: antineoplastic chemotherapy administration (96405, 96406, 96401, 96409, 96411, 96413, 96415, 96416, 96417, 96420, 96422, 96423, 96425, 96440, 96446, 96450, 96542), antineoplastic hormone therapy administration (96402), non-chemotherapy infusion (96360, 96361, 96365, 96366, 96367, 96368, 96369, 96370, 96371, 96372, 96373, 96374, 96375, 96376 ), bone marrow sampling (38220, 38221, 38222), bone marrow harvest (38230, 38232) and bone marrow transplant (38240, 38241, 38242). Consumer Price Index (CPI) obtained from the U.S. Department of Labor's Bureau of Labor Statistics was used to adjust reimbursement rates for cumulative inflation to 2022 U.S. dollars. The T-test was used to compare the mean prices for each procedure. This research contains publicly available data and as such is exempt from the IRB according to the Institutional Review Board at LSU Health Sciences Center in New Orleans, Louisiana. Results: The procedure with the highest reimbursement rate in 2012 was bone marrow harvest and the procedure with the lowest reimbursement rate in the same year was antineoplastic hormone therapy administration. The procedure with the highest reimbursement rate in 2022 was bone marrow harvest. The procedure with the lowest reimbursement rate in 2022 was antineoplastic hormone therapy. All procedure reimbursement fell significantly (p value of &lt;0.001) over the timer period studied. Conclusions: Between 2012 and 2022 the reimbursement rates for common hematology oncology services fell significantly when adjusted for inflation due to reforms in Medicare part B. [Table: see text]
The efficacy and safety of anlotinib combined with bevacizumab in treatment of recurrent isocitrate dehydrogenase wildtype glioblastoma: A retrospective analysis.
Authors: Shuo Li, Long Lai, Zhiwei Hou, Rongjie Tao, Bing Qu, Hui Zhang, Jinming Yu
Journal: Journal of Clinical Oncology (2023)

e14028 Background: Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor with a 5-year survival rate of 5%. There is no standard and effective treatment for recurrent GBM. Angiogenesis is recognized as a key event in the progression of GBM. Bevacizumab as an anti-angiogenic monoclonal antibody has been recommended by NCCN guidelines for recurrent GBM. Anlotinib is a small-molecule multi-target tyrosine kinase inhibitor (TKI) which has different function mechanisms and targets with bevacizumab. Therefore, we investigated the clinical efficacy and safety of anlotinib combined with bevacizumab in patients with recurrent IDH-wide type (wt) GBM on the basis of TMZ treatment. Methods: We retrospectively analyzed the clinical data of 18 patients with IDH-wt GBM in Shandong Cancer Hospital and Institute from 2019 to 2022. The primary endpoint was progression-free survival (PFS) and overall survival (OS) for combination treatment. The secondary endpoint was 6-months PFS rate, 1-year OS rate, objective response rate (ORR), disease control rate (DCR), OS and safety and toxicity profile. Results: All patients were diagnosed as WHO grade IV IDH-wt GBM and the median age of all patients was 55 years (range 39-76). Patients with recurrent GBM were first treated with anlotinib, followed by bevacizumab when patients developed progression or cerebral edema. In the overall population, the median OS for overall patients is 27 months, and the median survival time after first recurrence is 13.3 months. The median survival time of anlotinib treatment and combination treatment is 15.6 months and 12 months, respectively and the median PFS is 14.3 months and 9.1 months, respectively. The ORR for combination treatment was 27.8%, and 6-months DCR was 77.8%. The last follow-up date was October 15, 2022. By the last follow-up date, 3 patients were continuing anlotinib combined with bevacizumab treatment with no disease progression. The 6-months PFS rate was 78.9%, and the 1-year OS rate was 44.4%. The treatment-related adverse events (AEs) were shown in Table 3. The main AEs was bone marrow suppression (83.3%, 15/18), most of which were grade I and II (50%, 9). The AEs were relieved by adjusting the drug dose and symptomatic treatment. There were no treatment related deaths. Conclusions: Our study reported the clinical effect of anlotinib combined with bevacizumab treatment in recurrent GBM patients on the basis of TMZ treatment in a real-world setting. This is the first attempt to conduct dual antiangiogenic treatment in GBM patients. We demonstrate a promising result and suggest that this combination treatment may be a novel and safety treatment option for recurrent IDH-wt GBM patients.
Machine learning prediction of progression events in oncology RECIST 1.1 clinical trials.
Authors: Erin Bowman, Shyam Banuprakash, Kim Nguyen, Matthew Marini
Journal: Journal of Clinical Oncology (2023)

e13589 Background: Oncology clinical trials often have an imaging based surrogate endpoint such as Progression Free Survival (PFS). Using PFS as a surrogate for survival has the advantage of achieving trial completion more quickly which reduces cost and risk to patients. These trials are frequently structured to require a certain number of events to achieve statistical significance. The use of machine learning models which can make predictions about progression events from data obtained after the initiation of therapy is a novel idea in this field. It is well understood that many factors play a role in whether a patient will ultimately progress on a certain therapy. While certain statistical predictions can be made given known factors such as tumor genetics and patient history, these are made prior to the patient initiating therapy and do not consider on-therapy response. Machine learning models can be used during trial conduct, incorporate patient response, and better predict progression outcomes. Methods: Machine learning models were trained on over 115,000 RECIST 1.1 datapoints. The iterative training process included inputs from the medical science team which included a lead radiologist with expertise in diagnostic radiology and molecular imaging; and a lead medical informaticist responsible for data quality. Models were trained using 56 raw and derived features. Examples of derived features include number of lesions, time between evaluations, and change in responses over time. The features were trained using Random Forest, AdaBoost, Gradient Boost, XGBoost model types and compared to determine which one performed best. These model types identified the top predictors and created tree-based visuals, which provided insights into the model’s decision-making process. Confusion matrices were reviewed by the team to iteratively address false positive and false negative records. Results: Initial results of the machine learning model demonstrated a 75.1% specificity and a 66.6% accuracy for prediction of progression events. With continuous improvement efforts, as of writing, the model demonstrated 94.4% specificity, and 82.2% accuracy. This process identified the top predictors of progression to be the primary RECIST 1.1 features. Given our scientific and AI expertise results are expected to improve over time. Conclusions: Outcomes have shown the ability to predict RECIST 1.1 progression. Such a model could successfully predict when the required number of progression events are present within a population, at which point enrollment could be ceased and decrease overall trial length. Given enough data and rigorous testing, this technology could predict complete response vs partial response, adverse events, and time to events. Data suggests that AI machine learning within Clinical Trials could have a significant impact and should be considered a priority for continued evaluation given the possible benefits to trials.
Belzutifan treatment of Von Hippel-Lindau (VHL) related central nervous system (CNS) hemangioblastomas (HBs): A single institution experience.
Authors: Othon Iliopoulos, Otto Rapalino, Frederick G. Barker, Jean-Valery Coumans, Pamela Jones, Lauren Bear, Eumorphia Konstantakou, Christina Orr, Maura Mahar, Brian Nahed
Journal: Journal of Clinical Oncology (2023)

2078 Background: Patients with inactivating germline mutations in the VHL gene develop CNS (brain and/or spine) HBs and/or renal cancers, pheochromocytomas and pancreatic neuroendocrine tumors. The oral HIF2a inhibitor belzutifan has been approved by FDA for the treatment of VHL-related HBs. We present here data on a cohort of VHL patients with CNS HBs treated with belzutifan in a single institution. Methods: Adult VHL patients, with radiologically documented CNS (brain and/or spine) HBs that displayed documented growth within the last 6 months prior to therapy, were treated with an initial dose of 120 mg belzutifan orally per day. Target lesions included HBs &gt; 0.4cm long in one maximal cross-sectional diameter. Lesions were imaged by MRI at 1.5, 3, 6 months after initiation of treatment and at 6-month intervals thereafter. Solid enhancing lesions, associated cysts and peritumoral edema were recorded and quantified. Tumor sizes were evaluated by RECIST 1.1 criteria and volumetric analysis. All patients were evaluated and treated in the Hemangioblastoma Center and the VHL Clinic of the Massachusetts General Hospital Cancer Center. Results: At the time of analysis, 9 females and ten 10 male VHL patients (n=19) have been treated. Median age at treatment initiation was 36 yo (range 19-59). Median follow up is 12 months (range 1-19.5 months). Two patients were not yet evaluable for response. Of 17 evaluable patients, 8 had a PR (ORR 47%; 95% CI, 34-60), 8 had SD and 1 patient had progression (PD, 5.8%). Two patients had dose reduction to 80 mg/d because of anemia. No patient had grade 3 or greater toxicity and no patient experienced a CNS related toxicity during treatment. Volumetric analysis of solid and cystic components of the lesions, VHL germline mutations and other correlates of response to belzutifan will be presented. Conclusions: Real world data collected at a single institution confirm the high response rate of both solid and cystic components of CNS HBs to the FDA approved HIF2a inhibitor, belzutifan. Belzutifan was well tolerated. Further prospective controlled studies addressing the optimal dose, schedule and duration of treatment of HBs with belzutifan are required.
Assessing mail-in cryopreservation for fertility preservation.
Authors: Andre R Belarmino, Jerrine Morris, Stacey A. Kenfield, Daniel Colin, Bailey Griscom, Stanton Honig, James M. Dupree, Mary K. Samplaski, Joshua Halpern, Barry Behr, Dolores Lamb, William Matthews, James F. Smith
Journal: Journal of Clinical Oncology (2023)

1525 Background: Over 90% of oncologists agree that sperm banking should be offered to all men at risk of subfertility associated with cancer treatment, but fewer than 50% bring up the topic. Barriers cited include lack of time for the discussion, perceived high cost, and lack of convenient facilities. The advent of mail-in semen analysis (SA) testing and cryopreservation may improve access to this service via lower patient cost, decreased required oncologist logistical support, and home rather than local lab collection. That said, average sperm recovery rate after sample thaw is ~50% with immediate banking, and sperm recovery rate after delayed cryopreservation with a mail-in approach remains unknown. Methods: This is a prospective preliminary study assessing freeze-thaw total motile count at 3 time points of cryopreservation: upon receipt of sample, at 24 hours, and at 48 hours post collection. We collected 39 fresh semen samples from 13 healthy adult volunteers. Samples were diluted with 5mL of Fellow Health preservation solution and analyzed (World Health Organization guidelines V5). Samples were divided into 3 aliquots: Aliquot #1, T0 was immediately frozen with equal part cryoprotectant. Aliquot #2, T24 and aliquot #3, T48 were left at room temperature for 24 and 48 hrs respectively, analyzed, and then frozen. Aliquots were then thawed on a heat block at 37C for 10 minutes and analyzed. Results: Baseline SA values were: volume 3.3ml +/- 1.3, concentration 138.3 +/-57.4 x 10 6 , motility 49% +/-6%; Total Motile Count (TMC) 213 +/- 110 million. TMC was the primary endpoint as measured by baseline semen volume, concentration, and motility at 3 time points (T0, T24, T48). The average loss from freeze/thaw in TMC at T0 was 45%, at T24 was 55% relative to T24 pre-freeze, and at T48 was 59% relative to T48 pre-freeze (p = 0.013). On average, samples with starting TMC between 50-100 million had enough motile sperm for six intrauterine insemination (IUI) cycles when frozen and thawed at T0, two at T24, and two at T48. Samples with starting TMC between 100-200 million had enough motile sperm for 16 IUI cycles when frozen and thawed at T0, eight at T24, and four at T48. Samples with starting TMC &gt; 200 million had enough motile sperm for 42 IUI cycles when frozen and thawed at T0, 21 at T24, and nine at T48. All samples had ample viable cells ( &gt; 50,000) at all three time points for in vitro fertilization (IVF). Conclusions: Mail-in cryopreservation using our improved methodology may increase access to this service for oncological patients while still facilitating reasonable assisted reproductive technology care relative to in-person cryopreservation.
Longitudinal MRI-based radiomic model to complement sentinel lymph node biopsy assessment after neoadjuvant chemotherapy in initially clinically node-positive breast cancer: A multicentre, diagnostic study.
Authors: Kun Wang, Teng Zhu, Yuhong Huang, Wei Li
Journal: Journal of Clinical Oncology (2023)

e13623 Background: The high false-negative rate (FNR) of sentinel lymph node biopsy (SLNB) alone results in unnecessary axillary lymph node dissection (ALND) in initially clinically node-positive (cN+) breast cancer after neoadjuvant chemotherapy (NAC). This study aimed to reduce the FNR by establishing a longitudinal MRI radiomics-assisted SLNB model compared with SLNB alone. Methods: We established and tested a machine learning algorithm (RMLM) based on pre-NAC, post-NAC and longitudinal MRI radiomics features to detect axillary complete response (ypN0) to neoadjuvant chemotherapy in cN+ breast cancer. In total, 234 eligible patients who underwent SLNB and ALND were retrospectively recruited in the primary cohort (PC), 723 patients were in external validation cohorts (EVC) 1-3, and 81 patients from two multicentre prospective clinical trials (ClinicalTrials.gov, NCT03154749, NCT04858529) were enrolled in the prospective validation cohort (PVC). The U test and least absolute shrinkage and selection operator with tenfold cross-validation were used to select the most significant features. The specificity and FNR of RMLM-assisted SLNB were compared with those of SLNB alone. Results: In the primary (n=234 patients), external validation (n=723) and prospective validation sets (n=81), RMLM achieved excellent performance in detecting metastatic axillary lymph nodes (AUC=0.938 in the primary cohort, 0.842-0.913 in the external cohorts, 0.865 in the prospective validation cohort). RMLM-assisted SLNB achieved an FNR of 4.96% in PC, 5.83-8.08% in EVC1-3, and 9.09% in the prospective validation cohort. The removal of more than two SLNs combined with RMLM could further reduce the FNR to 2.78% in PC, 3.28-7.27% in EVC1-3, and 6.67% in the prospective validation cohort. Conclusions: RMLM combined with SLNB provides a potential tool to evaluate residual nodal disease after NAC and reduce unnecessary ALND.
Evaluating the impact of nurse navigation on high-risk breast clinic appointment uptake in a cancer risk assessment program.
Authors: Samantha Levin, Shirlene Paul, Chelsea McPeek, Rosalinda Alvarado, Mia Alyce Levy, Lisa Stempel
Journal: Journal of Clinical Oncology (2023)

e13510 Background: Patients in the breast imaging center are offered comprehensive cancer risk assessment (CRA) using validated risk assessment models (Tyrer-Cuzick 8, GAIL, and NCCN guidelines for genetic testing) at the time of screening mammography. All patients who receive a high-risk breast cancer score are recommended to follow-up at the high-risk breast clinic (HRBC) to determine a personalized management plan including MRI screening, genetic testing, and treatment options. Insufficient communication and patient education regarding breast cancer screening contributes to low HRBC appointment uptake. Nurse navigation (NN) was used to increase the HRBC appointment completion rate. This project aims to assess the effect of NN on HRBC appointment uptake in patients with a high-risk of breast cancer. Methods: Data regarding NN and HRBC appointment uptake for all women at a breast imaging center with a high-risk breast cancer score between July 2021 and January 2022 was extracted from the EMR and grouped into cohorts to assess the impact of NN on HRBC appointment completion. Family history of breast cancer, breast cancer risk model type, and insurance status were also extracted to analyze their relationships with HRBC appointment uptake. A chi-squared analysis was performed to assess the significance of the results. Results: NN contact and HRBC appointment completion of 4090 patients were analyzed. Of the 4090 patients, 1787 (43.7%) were successfully contacted by a nurse navigator. Patients with a family history of breast cancer were more likely to have contact with the nurse navigator (p = 0.022) and complete HRBC appointment (p = 0.017). The distribution of breast cancer risk model and distribution of insurance type were different for patients who completed HRBC appointments and those who did not, (p = 0.0012) and (p = 0.0027), respectively. Of the 4090 total patients, 122 (3.0%) attended the HRBC. Of the 1787 patients contacted by a nurse navigator, 80 (4.5%) completed HRBC appointments (p &lt; 0.0001). Conclusions: Coupling NN with a CRA program at the breast imaging center increased the number of qualified patients who completed HRBC appointments who would not have been identified prior to this program. Patients with a family history of breast cancer, certain types of breast cancer risk model, and certain types of insurance were found to have increased uptake of HRBC appointments. As a result, more patients will receive recommended supplemental screenings and management from a multidisciplinary care team.[Table: see text]